IMMUNOLOGICAL AND VIROLOGICAL CHANGES ASSOCIATED WITH DECLINE IN CD4 CD8 RATIOS IN LYMPHOID ORGANS OF SIV-INFECTED MACAQUES/

The decline in CD4/CD8 ratios in lymph nodes (LNs) of SIV macaques and HIV-infected individuals occurs later than that in blood. In a previo us study, long-term SIV-infected macaques were delineated into two gro ups: (1) those whose LNs had normal CD4/CD8 ratios and (2) those whose LNs had low CD4/CD8 ratios. In the present investigation, LNs, spleen s, and blood from these groups have been further analyzed to ascertain the cellular and virological events, particularly those involving CD8 (+) cells, that occur concomitantly with LN CD4% decline. An increase in the percent of CD69(-), IL-2R(p75)(-), CD45RA1o CD8(+) cells was th e most constant event observed in lymphoid tissue from mid- to late-st age SIV-infected monkeys. Such cells were sometimes observed in LNs pr ior to any other immunological or morphological changes. However, decl ine in LN CD4/CD8 ratios and the associated degeneration of follicular dendritic cells (FDCs) in the germinal centers (GCs) of these nodes w ere observed only when both CD8(+) cell infiltration of GCs and accumu lation of viral antigens within the FDC network could be demonstrated. These dramatic changes were also associated with significantly reduce d responsiveness to mitogens throughout the lymphoid compartment. In t erms of viral bur- den, immunological and structural collapse of LNs w as not always associated with increased viral DNA levels. Despite the CD4(+) cell decline in blood during HIV and SIV infections, the immuno logical and architectural collapse of the lymphoid compartment, which comprises the bulk of the lymphocytes in the body, appears to be a cri tical event leading to the onset of AIDS. The present findings suggest that increased CD8(+) cell activity as well as decrease in CD4(+) cel l function both contribute to this process.